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Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.ORCID iD: 0000-0001-6120-2683
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
2007 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 19, no 2, 285-291 p.Article in journal (Refereed) Published
Abstract [en]

The direct instillation of radiolabelled conjugates in the urinary bladder is a promising path for the treatment of bladder carcinoma. The targeting of HER2/neu receptors expressed on the surface of many bladder carcinoma cells shows potential to be developed as a therapeutic strategy, and patients identified with a high risk of progression may benefit from adjuvant targeted radionuclide therapy. A phage-display selected Affibody molecule (Z(HER2:342)) which binds to HER2/neu with picomolar affinity, can be used for targeting HER2/neu-expressing bladder carcinomas. A DOTA-derivative of Z(HER2:342), designated as DOTA-Z(HER2:342)-3, is considered as a suitable targeting agent for therapy. The DOTA chelator provides stable labelling with radiometals, and the low molecular weight (7.2 kDa) of the DOTA-Z(HER2:342)-3 compound is expected to enable efficient tumor penetration. DOTA-Z(HER2:342)-3 was radiolabelled with 90Y and 177Lu in 1 M ammonium acetate buffer, at pH 5.5, and in the presence of ascorbic acid. Nearly quantitative labelling yields were achieved for both nuclides after 15 min of incubation at 60 degrees C. After chelation, the conjugates retained their capacity to specifically bind to HER2/neu-expressing SKOV-3 cells. The radiolabelled affibody conjugate (DOTA-Z(HER2:342)-3) demonstrated high antigen-binding capacity and good cellular retention. Biodistribution in normal mice demonstrated low uptake in all organs and tissues except for kidneys.

Place, publisher, year, edition, pages
2007. Vol. 19, no 2, 285-291 p.
Keyword [en]
Animals, Cell Line; Tumor, Cell Survival/drug effects, Humans, Mice, Recombinant Fusion Proteins/pharmacokinetics/*therapeutic use, Urinary Bladder Neoplasms/*drug therapy/pathology, Yttrium Radioisotopes/pharmacokinetics/*therapeutic use
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104537ISI: 000243618900011PubMedID: 17203203OAI: oai:DiVA.org:uu-104537DiVA: diva2:219929
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2015-03-24Bibliographically approved

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Orlova, AnnaTolmachev, Vladimir

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